ORGANIC LETTERS
Highly Enantioselective Addition of Phenylacetylene to Aldehydes Catalyzed by a Camphorsulfonamide Ligand
2004 Vol. 6, No. 8 1193-1195
Zhaoqing Xu,† Chao Chen,† Jiangke Xu,† Mingbo Miao,† Wenjin Yan,† and Rui Wang*,†,‡ Department of Biochemistry and Molecular Biology, School of Life Science, Lanzhou UniVersity, Lanzhou 730000, China, and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking UniVersity, Beijing 100871, China
[email protected] Received December 12, 2003
ABSTRACT
The asymmetric addition of phenylacetylene to aldehydes was carried out by using a camphorsulfonamide titanium complex as a catalyst. The reactions proceeded under mild conditions and gave the products with good yields and high ees. This system is very useful for the synthesis of chiral propargylic alcohol.
The asymmetric addition of alkynyl regents to aldehydes is very useful for the synthesis of chiral secondary propargylic alcohols,1,2 which are very important building blocks for many chiral organic compounds.3 The acetylene and hydroxyl functions of the propargylic alcohol products can be used to construct very diverse molecular structures. Recently, Carreira reported that amino alcohol 1 can effectively catalyze * To whom correspondence should be addressed. † Lanzhou University. ‡ Peking University. (1) For review, see: (a)Pu, L.; Yu, H. B. Chem. ReV. 2001, 101, 757. (b) Frantz, D. E.; Fassler, R.; Tomooka, C. S.; Carreira, E. M. Acc. Chem. Res. 2000, 33, 373. (c) Pu, L. Tetrahedron 2003, 59, 9873. (2) Selected recent examples of our group: (a) Liu, D. X.; Zhang, L. C.; Wang, Q.; Da, C. S.; Xin, Z. Q.; Wang, R.; Choi, M. C. K.; Chan, A. S. C. Org. Lett. 2001, 3, 2733. (b) Yang, X. W.; Su, W.; Liu, D. X.; Wang, H. S.; Shen, J. H.; Da, C. S.; Wang, R.; Chan, A. S. C. Tetrahedron 2000, 56, 3511. (c) Yang, X. W.; Shen, J. H.; Da, C. S.; Wang, H. S.; Su, W.; Liu, D. X.; Wang, R.; Choi, M. C. K.; Chan, A. S. C. Tetrahedron Lett. 2001, 42, 6573. (d) Yang, X. W.; Shen, J. H.; Da, C. S.; Wang, H. S.; Su, W.; Wang, R.; Chan, A. S. C. J. Org. Chem. 2000, 65, 295. (e) Xu, Z.; Wang, R.; Xu, J.; Da, C.; Yan, W.; Chen, C. Angew. Chem., Int. Ed. 2003, 42, 5747. 10.1021/ol036418u CCC: $27.50 Published on Web 03/13/2004
© 2004 American Chemical Society
this reaction, but the substrates were limited in aliphatic aldehydes due to the significant Cannizzaro reaction.4 Pu reported that BINOL-Ti complex can catalyze alkynylzinc addition to both aromatic and aliphatic aldehydes with high ees and good yields. In his system, he used a separate step to synthesize alkynylzinc at high temperature.5 Chan reported that a 1:1 combination of BINOL 2 with sulfonamide as the ligand can also catalyze this reaction. The reactions were run at temperatures below 0 °C for 1-2 days and give the products with high ees.6 (3) (a) Marsh, J. A.; Wang, X. J. J. Org. Chem. 1992, 57, 1242. (b) Meyers, A. G.; Zhang, B. J. Am. Chem. Soc. 1996, 118, 4492. (c) Fox, M. E.; Li, C.; Marino, J. P., Jr.; Overman, L. E. J. Am. Chem. Soc. 1999, 121, 5467. (4) (a) Frantz, D. E.; Fassler, R.; Carreira, E. M. J. Am. Chem. Soc. 2000, 122, 1806. (b) Anand, N. K.; Carreira, E. M. J. Am. Chem. Soc. 2001, 123, 9687. (c) Boyall, D.; Frantz, D. E.; Carreira, E. M. Org. Lett. 2002, 4, 2605. (d) Boyall, D.; Lopez, F.; Sasaki, H.; Frantz, D. E.; Carreira, E. M. Org. Lett. 2000, 2, 4233. (e) El-Sayed, E.; Anand, N. K. Carreira, E. M. Org. Lett. 2001, 3, 3017. (5) (a) Gao, G.; Moore, D.; Xie, R. G.; Pu, L. Org. Lett. 2002, 4, 4143. (b) Xu M. H.; Pu, L. Org. Lett. 2002, 4, 4555.
Scheme 2.
Sulfonamide has the property that the N-H of sulfonamide is acidic due to the highly electron-withdrawing nature of the sulfonyl group. Therefore, unlike traditional metal amides (M-NR2), the sulfonamide nitrogen is a poor electron donor, and the resulting complexes are Lewis acidic.7 Camphor derivatives are among the most efficient chiral ligands reported in catalytic asymmetric reaction.8 We used (+)-camphor as a starting material. After four simple steps, we got a camphorsulfonamide in an overall yield of 42% (Scheme 1) and used it as a catalyst in the asymmetric addition of
Scheme 1.
Synthesis of the Camphorsulfonamide Ligand 79
Reaction of Phenylacetylene with Benzaldehyde in the Presence of Et2Zn, 7, and Ti(OiPr)410
Table 1. Asymmetric Addition of Phenylacetylene to Benzaldehyde Using 7 as a Liganda entry
ligand (mol %)
ligand/ Ti(OiPr)4b
Et2Zn (mol %)
solvent
temp
eec (%)
1 2 3 4 5 6 7 8 9 10
10% 10% 10% 10% 10% 2% 5% 10% 10% 10%
1/2 1/3 1/4 1/5 1/4 1/4 1/4 1/4 1/4 1/4
300 300 300 300 300 300 300 300 200 150
CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 toluene CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2
rt rt rt rt rt rt rt 0 °C rt rt
93 94 97 93 85 78 84 90 81 79
a Phenylacetylene/Et Zn ) 1:1. b Ti(OiPr) was freshly distilled. c Enan2 4 tiomeric excess was determined by HPLC analysis of the corresponding products on a Chiralcel OD column.
reaction from room temperature to 0 °C increased the reaction time and decreased the ee (entry 8). When we decreased the amount of Et2Zn from 300 to 200 and 150 mol %, the enantioselectivity also decreased (entries 9, 10). Under the above optimized reaction conditions, ligand 7 was employed to induce the enantioselective addition of phenylacetylene to a family of aldehydes. As the results summarized in Table 2 show, all the aromatic aldehydes afforded high enantioselectivities, and the aliphatic aldehydes also gave good ees.
Table 2. Asymmetric Addition of Phenylacetylene to Aldehydes Promoted by Ligand 7a-c
phenylacetylene to aldehydes. To our astonishment, this ligand can catalyze the reaction with high speed, under mild conditions, and in good yields, and the ee values are also high. Herein, we report our results. First, we tested it in the asymmetric addition of phenylacetylene to benzaldehyde in the presence of diethylzinc (Scheme 2). We found that the reaction was influenced by the amount of Ti(OiPr)4, and the ee was greatest when 7/Ti(OiPr)4 was 1/4 (Table 1, entries 1-4). The solvents also can influence the ees (entry 5). When the amount of the ligand was increased from 2 to 5% and 10%, the ee increased slightly (entries 6, 7). Decreasing the temperature of the (6) (a) Li, X. S.; Lu, G.; W. Kwok, H.; Chan, A. S. C. J. Am. Chem. Soc. 2002, 124, 12636. (b) Lu, G.; Li, X.; Chan, W. L.; Chan, A. S. C. Chem. Commun. 2002, 172. (7) Pritchett, S.; Gantzel, P.; Walsh, P. J. Organometallics 1997, 16, 5130. 1194
entry
aldehydes
time (h)
isolated yield (%)
ee (%)d
1 2 3 4 5 6 7 8 9 10 11 12 13
benzaldehyde 2-anisaldehyde 3-anisaldehyde 4-ansialdehyde 3-bromobenzaldehyde 4-bromobenzaldehyde 4-chlorobenzaldehyde 4-fluorohenzaldehyde R-naphthaldehyde β-naphthaldehyde cinnamicaldehyde butylaldehyde isobutylaldehyde
12 12 12 12 12 12 12 12 14 14 12 12 12
93 89 85 90 91 85 81 87 67 75 71 82 88
97 97 95 92 94 92 92 93 91 98 93 85 75
a In all of the entries, Et Zn/phenylacetylene/aldehyde/Ti(OiPr) /7 ) 3:3: 2 4 1:0.4:0.1. b All reactions were processed under argon and at room temperature. c Ti(OiPr)4was freshly distilled before use. d Ee values were determined by chiral HPLC with a Chiracel OD column.
Org. Lett., Vol. 6, No. 8, 2004
In conclusion, we have conveniently synthesized a sulfonamide ligand from natural camphor in four steps with good yield. The ligand is an excellent catalyst for the reaction of enantioselective addition of phenylacetylene to aldehydes under very mild conditions. In this system, severe conditions are not needed to prepare alkynylzinc in a separate step. This low-cost catalyst will substantially improve the availability of the reaction. Acknowledgment. This work was supported by the National Natural Science Foundation of China (No. 20372028), the Ministry of Science and Technology of China, the Teaching and Research Award Program for Outstanding Young Teachers, the Specialized Research Fund for the (8) For some selected examples of camphor derivatives, see: (a) Kitamura, M.; Suga, S.; Noyori, R. J. Am. Chem. Soc. 1986, 108, 6071. (b) Balsells, J.; Walsh, P. J. J. Am. Chem. Soc. 2000, 122, 3250. (c) Garcia, C.; LaRochelle, L. K.;Walsh, P. J. J. Am. Chem. Soc. 2002, 124, 10970.
Org. Lett., Vol. 6, No. 8, 2004
Doctoral Program in Higher Education Institutions, the Key Research Program of Science & Technology of the Ministry of Education of China, and the 985 Program of Lanzhou University of China. Supporting Information Available: Characterization of ligand 7 and the propargylic alcohols and procedures for addition of phenylacethylene to aldehydes. This material is available free of charge via the Internet at http://pubs.acs.org. OL036418U (9) Camphorsulfonylamino 7 was synthesized according to literature procedures: (a) Chittenden, R. A.; Cooper, G. H. J. Chem. Soc. C, 1970, 49. (b) You, J. S.; Shao, M. Y.; Gau, H. M. Tetrahedron: Asymmetry 2001, 12, 2971. (c) Itsuno, S.; Watanabe, K.; Matsunomo, T.; Kuroda, S.; Yokoi, A.; El-Shehawy, A. J. Chem. Soc., Perkin Trans. 1999, 1, 2011-2016. (10) Absolute configuration is based on measurement of the optical rotation and comparison with the literature values: Frantz, D. E.; Fassler, R.; Carreira, E. M. J. Am. Chem. Soc. 2000, 122, 1806.
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